A Catalytic Synthesis of Aziridines without the Usual Byproducts

Abstract

Complementary to existing routes, the Lewis acid catalyzed reactions of phenyldiazomethane with α-imino esters selectively produce cis-aziridine-2-carboxylates without competitive formation of enamino ester or carbene dimer byproducts.

catalysis - diazo compounds - heterocycles - imines - Lewis acids

References and Notes

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9

A couple catalytic aziridine-forming reactions of α-imino esters have been reported but none employ aryldiazo-methanes, see references 4h and 4x.

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11 We observed no polymerization of 4 in the presence of the imine. However, a solution of 4 has undergone slow polymerization (2-3 d) under similar conditions (2.3 mol% BF₃·Et₂O, 0.33 M 4 in toluene at -80 °C). For polymeri-zations of 4, see: Bawn CEH. Ledwith A. Matthies P. J. Polym. Sci.  1958,  33:  21 

12 Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides   Wiley; Toronto: 1998. also see references 4i, 5f, and 5i

13

The protic acid, TfOH, was recently found to be an effective catalyst for aziridine formation of imines with diazo acetates, see reference 4h.

14

Other reported catalytic aziridine syntheses that employ Yb(OTf)₃ use 10 mol%, presumably due to no optimization, see references: 4e, 4l, 4r, 4w, 4x, 4z, and 5c.

15

The only other report of a highly active Lewis acid catalyst in the synthesis of aziridines from imines with any diazo compound involves use of SnCl₄ (0.05 mol% for 50% conversion in 50 min), see reference 5a.

16

In these cases, an insufficient level of Lewis acid is present to selectively decompose the trans-aziridine isomer, as has been reported in reference 4m.

17 Bravo P. Capelli S. Crucianelli M. Guidetti M. Markovsky AL. Meille SV. Soloshonok VA. Sorochinsky AE. Viani F. Zanda M. Tetrahedron  1999,  55:  3025 

18

Typical Synthetic Procedure: To a CH₂Cl₂ solution (5 mL) of imine 3 (216 mg, 1.04 mmol) at -78 °C was added BF₃·Et₂O (5 mol%, 6.5 µL, 52 µmol) and the solution was stirred at -78 °C for 15 min. To this pale yellow solution was added, all at once, 4 (1.1 equiv, 327 µL of 3.5 M 4 in CH₂Cl₂) and stirring was continued for 1.5 h at -78 °C. The reaction flask was then removed from the -78 ºC bath and stirring was continued for another 45 min during which time the reaction mixture came to r.t. The reaction mixture was diluted with CH₂Cl₂ (5 mL), washed with a sat. aq solution of NaHCO₃ (3 × 10 mL), dried over Na₂SO₄ and filtered. The solvent was removed under reduced pressure to provide a yellow oil that was purified on silica gel by flash column chromatography using PE-EtOAc (from 95:5 to 85:15) to provide pure cis-5 [5f] (269.7 mg, 87%) as an off-white solid.

19 Taggi AE. Hafez AM. Lectka T. Acc. Chem. Res.  2003,  36:  10